12-O-tetradecanoylphorbol 13-acetate and forskolin modify muscarinic receptor-linked Ca2+ mobilization in SH-SY5Y neuroblastoma cells through different mechanisms.
The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), which causes differentiation of SH-SY5Y neuroblastoma cells, reduces carbachol binding and carbachol-stimulated Ca2+ mobilization in these cells. The decrease in responsiveness to carbachol is due partially to a reduction in the amount of Ca2+ released by the cells and partially to a decrease in the sensitivity of the cells to carbachol. These effects probably can be attributed to a reduction in muscarinic receptor number and a decrease in receptor affinity, respectively. Forskolin, an alkaloid known to cause an increase in cellular cyclic AMP, enhances Ca2+ influx into the cells without affecting the cytosolic free Ca2+ concentration. The alkaloid causes an apparent restoration of the reduced Ca2+ release, caused by TPA, but does not affect the sensitivity of the cells to carbachol. Forskolin increases the decay of carbachol-induced increase in cytosolic Ca2+. The effects of TPA appear to be linked directly to receptor function, whereas those of forskolin are due to the effect of cyclic AMP on cellular Ca2+ metabolism.
Akerman
K E
KE
Department of Biochemistry and Pharmacy, Abo Akademi, Finland.
Heikkilä
J E
JE
D001572:Benzofurans; D001667:Binding, Competitive; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials; D019832:N-Methylscopolamine; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009994:Osmolar Concentration; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D005456:Fluorescent Dyes; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D005576:Colforsin; D015759:Ionomycin; D002217:Carbachol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016257:Fura-2; D019832:N-Methylscopolamine